Síntese de tetrahidroquinolinas a partir da D-eritrose

Dissertação de mestrado em Química Medicinal

Full Exploration of the Diels–Alder Cycloaddition on Metallofullerenes M3N@C80 (M=Sc, Lu, Gd): The D5h versus Ih Isomer and the Influence of the Metal Cluster

In this work a detailed investigation of the exohedral reactivity of the most important and abundant endohedral metallofullerene (EMF) is provided, that is, Sc3N@Ih-C80 and its D5h counterpart Sc3N@D5h-C80, and the (bio)chemically relevant lutetium- and gadolinium-based M3N@Ih/D5h-C80 EMFs (M=Sc, Lu, Gd). In particular, we analyze the thermodynamics and kinetics of the Diels–Alder cycloaddition of s-cis-1,3-butadiene on all the different bonds of the Ih-C80 and D5h-C80 cages and their endohedral derivatives. First, we discuss the thermodynamic and kinetic aspects of the cycloaddition reaction on the hollow fullerenes and the two isomers of Sc3N@C80. Afterwards, the effect of the nature of the metal nitride is analyzed in detail. In general, our BP86/TZP//BP86/DZP calculations indicate that [5,6] bonds are more reactive than [6,6] bonds for the two isomers. The [5,6] bond D5h-b, which is the most similar to the unique [5,6] bond type in the icosahedral cage, Ih-a, is the most reactive bond in M3N@D5h-C80 regardless of M. Sc3N@C80 and Lu3N@C80 give similar results; the regioselectivity is, however, significantly reduced for the larger and more electropositive M=Gd, as previously found in similar metallofullerenes. Calculations also show that the D5h isomer is more reactive from the kinetic point of view than the Ih one in all cases which is in good agreement with experiments

Rhodium(I) catalyzed [2+2+2] cycloaddition reactions: experimental and theoretical studies

The [2+2+2] cycloaddition reaction involves the formation of three carbon-carbon bonds in one single step using alkynes, alkenes, nitriles, carbonyls and other unsaturated reagents as reactants. This is one of the most elegant methods for the construction of polycyclic aromatic compounds and heteroaromatic, which have important academic and industrial uses. The thesis is divided into ten chapters including six related publications. The first study based on the Wilkinson’s catalyst, RhCl(PPh3)3, compares the reaction mechanism of the [2+2+2] cycloaddition process of acetylene with the cycloaddition obtained for the model of the complex, RhCl(PH3)3. In an attempt to reduce computational costs in DFT studies, this research project aimed to substitute PPh3 ligands for PH3, despite the electronic and steric effects produced by PPh3 ligands being significantly different to those created by PH3 ones. In this first study, detailed theoretical calculations were performed to determine the reaction mechanism of the two complexes. Despite some differences being detected, it was found that modelling PPh3 by PH3 in the catalyst helps to reduce the computational cost significantly while at the same time providing qualitatively acceptable results. Taking into account the results obtained in this earlier study, the model of the Wilkinson’s catalyst, RhCl(PH3)3, was applied to study different [2+2+2] cycloaddition reactions with unsaturated systems conducted in the laboratory. Our research group found that in the case of totally closed systems, specifically 15- and 25-membered azamacrocycles can afford benzenic compounds, except in the case of 20-membered azamacrocycle (20-MAA) which was inactive with the Wilkinson’s catalyst. In this study, theoretical calculations allowed to determine the origin of the different reactivity of the 20-MAA, where it was found that the activation barrier of the oxidative addition of two alkynes is higher than those obtained for the 15- and 25-membered macrocycles. This barrier was attributed primarily to the interaction energy, which corresponds to the energy that is released when the two deformed reagents interact in the transition state. The main factor that helped to provide an explanation to the different reactivity observed was that the 20-MAA had a more stable and delocalized HOMO orbital in the oxidative addition step. Moreover, we observed that the formation of a strained ten-membered ring during the cycloaddition of 20-MAA presents significant steric hindrance. Furthermore, in Chapter 5, an electrochemical study is presented in collaboration with Prof. Anny Jutand from Paris. This work allowed studying the main steps of the catalytic cycle of the [2+2+2] cycloaddition reaction between diynes with a monoalkyne. First kinetic data were obtained of the [2+2+2] cycloaddition process catalyzed by the Wilkinson’s catalyst, where it was observed that the rate-determining step of the reaction can change depending on the structure of the starting reagents. In the case of the [2+2+2] cycloaddition reaction involving two alkynes and one alkene in the same molecule (enediynes), it is well known that the oxidative coupling may occur between two alkynes giving the corresponding metallacyclopentadiene, or between one alkyne and the alkene affording the metallacyclopentene complex. Wilkinson’s model was used in DFT calculations to analyze the different factors that may influence in the reaction mechanism. Here it was observed that the cyclic enediynes always prefer the oxidative coupling between two alkynes moieties, while the acyclic cases have different preferences depending on the linker and the substituents used in the alkynes. Moreover, the Wilkinson’s model was used to explain the experimental results achieved in Chapter 7 where the [2+2+2] cycloaddition reaction of enediynes is studied varying the position of the double bond in the starting reagent. It was observed that enediynes type yne-ene-yne preferred the standard [2+2+2] cycloaddition reaction, while enediynes type yne-yne-ene suffered β-hydride elimination followed a reductive elimination of Wilkinson’s catalyst giving cyclohexadiene compounds, which are isomers from those that would be obtained through standard [2+2+2] cycloaddition reactions. Finally, the last chapter of this thesis is based on the use of DFT calculations to determine the reaction mechanism when the macrocycles are treated with transition metals that are inactive to the [2+2+2] cycloaddition reaction, but which are thermally active leading to new polycyclic compounds. Thus, a domino process was described combining an ene reaction and a Diels-Alder cycloaddition.

A further exploration of a nucleophilicity index based on the gas-phase ionization potentials

An empirical nucleophilicity index based on the gas-phase ionization potentials has been recently shown to be useful categorizing and settling the nucleophilicity power of a series of captodative ethylenes reacting in cycloaddition reactions (L.R. Domingo, E. Chamorro, P. Perez, Journal of Organic Chemistry 73 (2008) 4615-4624). In the present work, the applicability of such model is tested within a broader series of substituted alkenes, substituted aromatic compounds and simple nucleophilic molecules. This index obtained within a Koopman`s theorem framework has been evaluated here in both gas and solution phases for several well-known nucleophiles. These results are found to be linearly correlated. Finally, the feasibility of the predictive character of this index has been discussed in comparison to the available experimental nucleophilicities of some amines in water. These results further support and validate the usefulness of such approximation in the modeling of the global nucleophilicity. (C) 2008 Elsevier B.V. All rights reserved.

Synthese und Reaktivität styrylsubstituierter p-Benzochinone

Synthese und Reaktivität styrylsubstituierter p-Benzochinone Oligo- und Poly(1,4-phenylenvinylene) (OPV, PPV) stellen eine für die Materialwissenschaft äußerst interessante Verbindungsklasse dar, die in Form von Halbleitern, Photoleitern, elektrolumineszierenden Systemen und negativen Photoresists breitgefächerte Anwendung findet. Allerdings stellt die Alterung dieser Materialien in Gegenwart von Sauerstoff und anderen Oxidationsmitteln ein signifikantes Problem dar. So wird z. B. die technische Anwendung von Leuchtdioden auf Polymerbasis durch ihre geringe Betriebsdauer eingeschränkt. Als Beitrag zur Untersuchung des oxidativen Abbaus von Poly- bzw. Oligo(p-phenylenvinylenen) [PPV, OPV] wurden verschiedene 2-Styryl-1,4-benzochinone - sowie höhere Oligomere - synthetisiert, die das Strukturelement einer hoch oxidierten Form von OPV's aufweisen. Durch Einführung einer Cyanogruppe an der olefinischen Doppelbindung wurde die Reaktivität der Modellsysteme gezielt beeinflußt. Die 2-Styryl-1,4-benzochinone mit unsubstituierter Doppelbindung dimerisieren in Lösung quantitativ im Sinne von Diels-Alder-Reaktionen zu den entsprechenden Cycloaddukten. Die Dimerisierungen verlaufen chemo-, regio- und stereoselektiv, was sich anhand von Grenzorbital-Betrachtungen erklären läßt.An der Oberfläche von Kieselgel erfolgt eine vollständige Umwandlung der Dimere, deren zwei Hauptprodukte identifiziert werden konnten: Neben Verbindungen, die durch eine intramolekulare [4+2]-Cycloaddition nach erfolgter Dehydrierung / Oxidation gebildet werden, entstehen verschiedene Additionsprodukte der Dimere mit Nucleophilen (Wasser, Ethanol). Cyanosubstitution führt bereits bei den als Vorstufe dienenden Stilbenen zu einer erleichterten (E/Z)-Photoisomerisierung in Lösung, die zu einem photostationären Gleichgewicht führt, welches sich durch einen hohen Anteil der (E)-Konfiguration auszeichnet. Nach erfolgter Oxidation kann ebenfalls eine Dimerisierung beobachtet werden. Bei direkter Nachbarschaft der Cyanogruppe zum Chinonring erfolgt stattdessen ein intramolekularer Ringschluß unter Ausbildung eines Benzofuranderivats.Die beobachtete Reaktivität der synthetisierten Chinonsysteme steht in Einklang mit einem möglichen sekundären Abbaumechanismus, der nach primärer Oxidation zu der Alterung von PPV's beitragen kann.

Synthesis and application of new ion-tagged ligands and organocatalysts

We report the synthesis and application of some ion-tagged catalysts in organometallic catalysis and organocatalysis. With the installation of an ionic group on the backbone of a known catalyst, two main effects are generally obtained. i) a modification of the solubility of the catalyst: if judicious choice of the ion pair is made, the ion-tag can confer to the catalyst a solubility profile suitable for catalyst recycling. ii) the ionic group can play a non-innocent role in the process considered: if stabilizing interaction between the ionic group and the developing charges in the transition state are established, the reaction can speed up. We describe the use of ion-tagged diphenylprolinol as Zn ligand. The chiral ligand grafted onto an ionic liquid (IL) was recycled 10 times with no loss of reactivity and selectivity, when it was employed in the first example of enantioselective addition of ZnEt2 to aldehydes in ILs. An ammonium-tagged phosphine displayed the capability to stabilize Pd catalysts for the Suzuki reaction in ILs. The ionic phase was recycled 6 times with no detectable loss of activity and very low Pd leaching in the organic phase. This catalytic system was also employed for the functionalization of the challenging substrate 5,11-dibromotetracene. In the field of organocatalysis, we prepared two ion-tagged derivatives of the McMillan imidazolidinone. The results of the asymmetric Diels-Alder reaction between trans-cinnamaldehyde and cyclopentadiene exhibited great dependence on the position and nature of the ionic group. Finally, when O-TMS-diphenylprolinol was tagged with an imidazolium ion, exploiting a silyl ether linker, an efficient catalyst for the asymmetric addition of aldehydes to nitroolefins was achieved. The catalyst displayed enhanced reactivity and the same high level of selectivity of the untagged parent catalyst and it could be employed in a wide range of reaction conditions, included use of water as solvent.

Polyphenylene dendrimers

The main goals of this work were the design, synthesis, and characterization of new functional polyphenylene dendrimers. Polyphenylene dendrimers are highly branched, monodisperse macromolecules consisting exclusively of benzene rings. They can be obtained in high yield by a repetitive Diels-Alder cycloaddition - deprotection protocol. Their shape-persistent dendritic scaffold allows to obtain nanoparticles with functional groups in defined relative orientation. In the first chapter polyphenylene dendrimers with a pyrene core are presented. The focus of the investigations was upon the shielding efficiency of dendritic shells of different generations upon the pyrene-functionality in the core. The herein presented materials combine high quantum efficiency, good solubility and improved film forming properties making them possible candidates for several applications in electronic devices. The defined functionalization of polyphenylene dendrimers often requires a great synthetic effort, since for every desired function the appropriate building block has to be synthesized. To overcome these disadvantages, a new functionalization concept based upon benzophenone precursors has been developed. This new concept has successfully been applied for the functionalization of the dendritic core, the dendrimer shell, and the dendrimer surface. To investigate the accessibility and reactivity of the embedded groups, many functions of different size and nature were introduced. Moreover, suitable precursors for the synthesis of dendrimer entrapped species, trityl cations, trityl radicals, and ketyl radical anions, were obtained. The combination of the synthetic protocols of core- and surface-functionalization resulted in a new type of functional molecules, highly interesting from the point of electron transfer processes. A polyphenylene dendron was used to arrange a triphenylamine donor and a perylene acceptor moiety in a defined spatial distance and orientation. The in-depth photophysical investigation of a first model compound is reported. The herein presented functionalized dendrimers are highly interesting as well from the point of view of fundamental research (looking into the optic and electronic properties of such unique shape persistent structures) as from the point of view of their potential application as tailor-made nanomaterials in the field of optoelectronics.

From pyrene to large polycyclic aromatic hydrocarbons

Studies of polycyclic aromatic hydrocarbons have shown that the overall size, periphery, and functionalization of PAHs are crucial parameters which significantly alter their electronic structure and chemical reactivity. Therefore, the major direction of this thesis is the synthesis and characterization of extended PAHs: (i) with different functional groups improving their processability, (ii) with different periphery changing their chemical reactivity, (iii) with inclusions of different metal ions, which influence their physical properties. • The cyclodehydrogenation reaction has been proposed for to synthesise polyphenylene ribbons with preplanarized (dibenzo[e,l]pyrene) moieties in the aromatic core with up to 10 nm linear size. The synthetic strategy employed is discussed in Chapter 2 and is based on stoichiometrically controlled DIELS-ALDER cycloaddition. All molecules possessed very good solubility in common organic solvents allowing their characterization by standard analytical techniques. • A new concept was developed to extend PAH’s core. Here the introduction of “zigzag” sites, discussed in Chpater 3 was shown to lower the HOMO-LUMO gap and to result in higher chemical reactivities. This allowed, in Chapters 3, 4 and 5, further functionalization of PAH and enlargement of their aromatic cores up to 224 atoms. Despite the size of these novel molecules, extraordinary solubilities in common organic solvents were obtained due to distortions from planarity of the aromatic cores by bulky tert-butyl groups, which hampered the usually very pronounced aggregation tendency of extended π-systems. All extended PAHs posses the small HOMO-LUMO gap together with good electron affinities making them potential candidates for application in organic FETs. • Another alternative synthetic route has been proposed to obtain extended the metal-PAH complexes. Using the quinoxaline methodology in Chapter 5 three new phenanthroline ligands (up to 60 skeletal atoms) have been synthesized and characterized. Four different (Ru(II), Cu(II) and Pt(II)) complexes were synthesized, allowing to construct a range of large metal complexes by varying the metal as well as the number and nature of ligands.

Novel Photochemical Methodologies For Diversity Oriented Synthesis And Screening Of Combinatorial Libraries

The main goal of this project was to develop an efficient methodology allowing rapid access to structurally diverse scaffolds decorated with various functional groups. Initially, we discovered and subsequently developed an experimentally straightforward, high-yielding photoinduced conversion of readily accessible diverse starting materials into polycyclic aldehydes and their (hemi)acetals decorated by various pendants. The two step sequence, involving the Diels-Alder addition of heterocyclic chalcones and other benzoyl ethylenes to a variety of dienes, followed by the Paternò-Büchi reaction, was described as an alkene-carbonyl oxametathesis. This methodology offers a rapid increase in molecular complexity and diversity of the target scaffolds. To develop this novel methodology further and explore its generality, we directed our attention to the Diels-Alder adducts based on various chromones. We discovered that the Diels-Alder adducts of chromones are capable of photoinduced alkene-arene [2+2] cycloaddition producing different dienes, which can either dimerize or be introduced into a double-tandem [4π+2π]·[2π+2π]·[4π+2π]·[2π+2π] synthetic sequence, followed by an acid-catalyzed oxametathesis, leading to a rapid expansion of molecular complexity over a few experimentally simple steps. In view of the fact that oxametathesis previously was primarily observed in aromatic oxetanes, we decided to prepare model aliphatic oxetanes with a conformationally unconstrained or "flexible" methyl group based on the Diels-Alder adducts of cyclohexadiene or cyclopentadiene with methyl vinyl ketone. Upon addition of an acid, the expected oxametathesis occurred with results similar to those observed in the aromatic series proving the generality of this approach. Also we synthesized polycyclic oxetanes resulting from the Diels-Alder adducts of cyclic ketones. This not only gave us access to remarkably strained oxetane systems, but also the mechanism for their protolytic ring opening provided a great deal of insight to how the strain affects the reactivity. Additionally, we discovered that although the model Hetero-Diels-Alder adducts did not undergo [2+2] cycloaddition, both exo- and endo-Sulfa-Diels-Alder products, nonetheless, were photochemically active and various products with defined stereochemistry could be produced upon photolysis. In conclusion, we have developed an approach to the encoding and screening of solution phase libraries based on the photorelease of externally sensitized photolabile tags. The encoding tags can be released into solution only when a binding event occurs between the ligand and the receptor, equipped with an electron transfer sensitizer. The released tags are analyzed in solution revealing the identity of the lead ligand or narrowing the range of potential leads.

Synthesis of xanthone-1,2,3-triazole dyads

Xanthones and 1,2,3-triazoles are known to exhibit several biological, pharmacological and biocidal properties[1]. The potential applications of these two classes of heterocycles led us to develop new strategies to synthesize xanthone-1,2,3-triazole dyads, aiming to get potentially improved therapeutic agents[2]. With this rational in mind we designed and synthesized novel chromone derivatives 1a-d to be used as building motifs and to explore the reactivity of the two unsaturated systems (the diene and the alkyne). In the present communication we will present a new synthetic route towards the synthesis of xanthone-1,2,3-triazole dyads 7a-d using consecutively the azide-alkyne Huisgen 1,3-dipolar cycloaddition and Diels-Alder reaction. Our approach involves the synthesis chromone-triazole derivatives 2a-d using the reaction of 1a-d with sodium azide, followed by the methylation of the NH of the triazole moiety. The methylation afforded three isomers 3a-d, 4a-d and 5a-d, as expected. The major isomers 3a-d were used in the Diels-Alder reaction with N-methylmaleimide, and the adducts obtained 6a-d were oxidized to afford the xanthone-1,2,3-triazole dyads 7a-d. All the synthetic details as well as the structural characterization (by 1D and 2D NMR studies) of the new synthesised compounds will be presented and discussed.

Cycloadditions of isobenzofuran to a constrained template bearing neighboring dienophiles

A high yielding synthesis of the pentacyclic diene-dione 1 has enabled investigation of its reactivity as a double dienophile in Diels-Alder [4+2] cycloadditions with isobenzofuran, leading to novel and highly symmetrical three-sided cavitands 3 and 4.

Synthesis and Properties of a Series of 1,1,n,n-Tetramethyl[n](2,11)teropyrenophanes

The work described in this thesis revolves around the 1,1,n,ntetramethyl[n](2,11)teropyrenophanes, which are a series of [n]cyclophanes with a severely bent, board-shaped polynuclear aromatic hydrocarbons (PAH). The thesis is divided into seven Chapters. The first Chapter conatins an overview of the seminal work on [n]cyclophanes of the first two members of the “capped rylene” series of PAHs: benzene and pyrene. Three different general strategies for the synthesis of [n]cyclophanes are discussed and this leads in to a discussion of some slected syntheses of [n]paracyclopahnes and [n](2,7)pyrenophanes. The chemical, structural, spectroscopic and photophysical properties of these benzene and pyrene-derived cyclophanes are discussed with emphasis on the changes that occur with changes in the structure of the aromatic system. Chapter 1 concludes with a brief introduction to [n]cyclophanes of the fourth member of the capped rylene series of PAHs: teropyrene. The focus of the work described in Chapter 2 is the synthesis of of 1,1,n,ntetramethyl[n](2,11)teropyrenophane (n = 6 and 7) using a double-McMurry strategy. While the synthesis 1,1,7,7-tetramethyl[7](2,11)teropyrenophane was successful, the synthesis of the lower homologue 1,1,6,6-tetramethyl[6](2,11)teropyrenophane was not. The conformational behaviour of [n.2]pyrenophanes was also studied by 1H NMR spectroscopy and this provided a conformation-based rationale for the failure of the synthesis of 1,1,6,6-tetramethyl[6](2,11)teropyrenophane. Chapter 3 contains details of the synthesis of 1,1,n,n-tetramethyl[n](2,11)teropyrenophanes (n = 7-9) using a Wurtz / McMurry strategy, which proved to be more general than the double McMurry strategy. The three teropyrenophanes were obtained in ca. 10 milligram quantities. Trends in the spectroscopic properties that accompany changes in the structure of the teropyrene system are discussed. A violation of Kasha’s rule was observed when the teropyrenophanes were irradiated at 260 nm. The work described in the fourth Chapter concentrates on the development of gram-scale syntheses of 1,1,n,n-tetramethyl[n](2,11)teropyrenophanes (n = 7–10) using the Wurtz / McMurry strategy. Several major modifications to the orginal synthetic pathway had to be made to enable the first several steps to be performed comfortably on tens of grams of material. Solubility problems severely limited the amount of material that could be produced at a late stage of the synthetic pathways leading to the evennumbered members of the series (n = 8, 10). Ultimately, only 1,1,9,9- tetramethyl[9](2,11)teropyrenophane was synthesized on a multi-gram scale. In the final step in the synthesis, a valence isomerization / dehydrogenation (VID) reaction, the teropyrenophane was observed to become unstable under the conditions of its formation at n = 8. The synthesis of 1,1,10,10-tetramethyl[10](2,11)teropyrenophane was achieved for the first time, but only on a few hundred milligram scale. In Chapter 5, the results of an investigation of the electrophilic aromatic bromination of the 1,1,n,n-tetramethyl[n](2,11)teropyrenophanes (n = 7–10) are presented. Being the most abundant cyclophane, most of the work was performed on 1,1,9,9-tetramethyl[9](2,11)teropyrenophane. Reaction of this compound with varying amounts of of bromine revealed that bromination occurs most rapidly at the symmetryrelated 4, 9, 13 and 18 positions (teropyrene numbering) and that the 4,9,13,18- tetrabromide could be formed exclusively. Subsequent bromination occurs selectively on the symmetry-related 6, 7, 15 and 16 positions (teropyrene numbering), but considerably more slowly. Only mixtures of penta-, hexa-, hepta and octabromides could be formed. Bromination reactions of the higher and lower homologues (n = 7, 8 and 10) revealed that the reactivity of the teropyrene system increased with the degree of bend. Crystal structures of some tetra-, hexa-, hepta- and octa-brominated products were obtained. The goal of the work described in Chapter 6 is to use 1,1,9,9- tetramethyl[9](2,11)teropyrenophane as a starting material for the synthesis of warped nanographenophanes. A bromination, Suzuki-Miyaura, cyclodehydrogenation sequence was unsuccessful, as was a C–H arylation / cyclodehydrogenation approach. Itami’s recently-developed K-region-selective annulative -extension (APEX) reaction proved to be successful, affording a giant [n]cyclophane with a C84 PAH. Attempted bay-region Diels-Alder reactions and some cursory host-guest chemistry of teropyrenophanes are also discussed. In Chapter 7 a synthetic approach toward a planar model compound, 2,11-di-tbutylteropyrene, is described. The synthesis could not be completed owing to solubility problems at the end of the synthetic pathway.

Synthesis of new amphiphilic chlorin derivatives from protoporphyrin-IX dimethyl ester

A simple synthesis of new amphiphilic chlorin derivatives from protoporphyrin-IX dimethyl ester is reported.The preparation Of Such compounds is based in a straightforward methodology, which involves the Diels-Alder reaction of protoporphyrin-IX dimethyl ester with maleic anhydride followed by addition of nucleophilic species to the initially formed cycloadducts, a transformation, which is highly regioselective. Preliminary photophysical studies with the new compounds show that they meet adequate features for PDT applications. (c) 2008 Elsevier Ltd. All rights reserved.

Fast and efficient synthesis of pyrano[3,2-c]quinolines catalyzed by niobium(V) chloride

A highly efficient two-step method for the synthesis of pyranoquinoline derivatives from imino-Diels-Alder reactions between aldimines and 3,4-dihydro-2H-pyran using niobium(V) chloride as catalyst under mild conditions is described.

Recognition of cyclic, acyclic, exocyclic, and spiro Acetals via structurally diagnostic ion/molecule reactions with the (CH3)(2)N-C+=O acylium ion

Reactions of the model acylium ion (CH3)(2)N-C+=O with acyclic, exocyclic, and Spiro acetals of the general formula (RO)-O-1-(CRR4)-R-3-OR2-upole mass spectrometry. Characteristic intrinsic reactivities were observed for each of these classes of acetals. The two most Characteristic intrinsic reactivities were observed for each of these classes of acetals. The two most common reactions observed were hydride and alkoxy anion [(RO-)-O-1 and (RO-)-O-2] abstraction. Other specific reactions were also observed: (a) a secondary polar [4(+) + 2] cycloaddition for acetals bearing alpha,beta-unsaturated R-3 or R-4 substituents and (b) OH- abstraction for exocyclic and spiro acetals. These structurally diagnostic reactions, in conjunction with others observed previously for cyclic acetals, are shown to reveal the class of the acetal molecule and its ring type and substituents and to permit their recognition and distinction from other classes of isomeric molecules.